Electrical synapses are fast (essentially no synaptic delay) and bidirectional (i.e., current generated in either cell can flow across the gap junction to influence the other cell). In addition they act as low-pass filters. That is, slow electrical events are much more readily transmitted than are fast signals such as action potentials. One important role for neuronal gap junctions appears to be synchronization of network activity. For example, the activity of inferior olivary neurons is normally synchronized but becomes uncorrelated when pharmacological blockers of gap junctions are injected into the inferior olive. It also appears that the patterns of electrical coupling by gap junctions may be highly specific. For example, neocortical interneurons almost exclusively couple to interneurons of the same type. This specific gap junction–coupling pattern suggests that multiple, independent, electrically coupled networks of interneurons may coexist across the neocortex.
Finally, although electrical synapses are generally regarded as relatively simple and static in comparison to chemical synapses, they may actually be fairly dynamic entities. For example, the properties of electrical synapses can be modulated by several factors, including voltage, intracellular pH, and [Ca++]. Moreover, they are subject to regulation by G protein–coupled receptors, and connexins (the protein subunits that form a gap junction, see
At The Cellular ) contain sites for phosphorylation. These factors can change the coupling between cells by causing changes in single-channel conductance, formation of new gap junctions, or removal of existing ones.
Chemical synaptic transmission was first demonstrated between the vagus nerve and the heart by a simple experiment by Otto Loewi. The vagus nerve of a frog was stimulated to slow the heart rate down while the solution perfusing the heart was collected. This solution was then used to perfuse a second heart, whose beating then also slowed, demonstrating that the vagal nerve stimulation had caused a chemical to be released into the solution. The chemical responsible was found to be acetylcholine, which we now know is also a neurotransmitter at the neuromuscular junction and at other synapses in the peripheral and central nervous systems.
Unlike the situation at electrical synapses, at chemical synapses there is no direct communication between the cytoplasm of the two cells. Instead the cell membranes are separated by a synaptic cleft of some 20 nm, and interaction between the cells occurs via chemical intermediaries known as neurotransmitters. Chemical synapses are generally unidirectional, and thus one can refer to the presynaptic and postsynaptic elements that are diagramed in
Fig. 6.2.
The presynaptic element is often the terminal portion of an axon and is packed with small vesicles whose exact shape and size vary with the neurotransmitter they contain. In addition, the presynaptic membrane apposed to the postsynaptic element has regions, known as active zones, of electron-dense material that corresponds to the proteins involved in transmitter release (see
Fig. 6.1B). Moreover, mitochondria and rough endoplasmic reticulum are typically found in the presynaptic terminal. The postsynaptic membrane is also characterized by electron-dense material, which in this case corresponds to the receptors for the neurotransmitter.
Chemical synapses occur between different parts of neurons. Traditionally, focus has been placed on synapses formed by an axon onto the dendrites or soma of a second cell (axodendritic or axosomatic synapses), and our description will be based primarily on such synapses. However, there are many additional types of chemical synapses, such as axoaxonic (axon to axon), dendrodendritic (dendrite to dendrite), and dendrosomatic (dendrite to soma). Furthermore, complex synaptic arrangements are possible, such as mixed synapses, in which cells form both electrical and chemical synapses with each other; serial synapses, in which an axoaxonic synapse is made onto the axon terminal and influences the efficacy of that terminal’s synapse with yet a third element; and reciprocal synapses, in which both cells can release transmitter to influence the other.